tbuckley/cabot-search huggingface dataset:
Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
Authors: Raoul C. Reulen, David L. Winter, Ibrahim Diallo, Cristina Veres, Damien Llanas, Rodrigue S. Allodji, Francesca Bagnasco, Edit Bárdi, Elizabeth A.M. Feijen, Daniela Alessi, Miranda M. Fidler-Benaoudia, Stine Høgsholt, Jop C. Teepen, Helena Linge, Nadia Haddy, Julianne Byrne, Ghazi Debiche, Desiree Grabow, Thorgerdur Gudmundsdottir, Romain Fauchery, Wael Zrafi, Gisela Michel, Hilde Øfstaas, Peter Kaatsch, Giao Vu-Bezin, Helen Jenkinson, Melanie Kaiser, Roderick Skinner, Trevor Cole, Nicolas Waespe, Grit Sommer, Susanne Nordenfelt, Momcilo Jankovic, Tuomas Lähteenmäki Taalas, Milena M. Maule, Helena J.H. van der Pal, Cécile M. Ronckers, Flora E. van Leeuwen, Judith L. Kok, Monica Terenziani, Maria Winther Gunnes, Thomas Wiebe, Carlotta Sacerdote, Zsuzsanna Jakab, Riccardo Haupt, Päivi M. Lähteenmäki, Lorna Zadravec Zaletel, Claudia E. Kuehni, Jeanette F. Winther, Leontien C.M. Kremer, Lars Hjorth, Florent de Vathaire, Michael M. Hawkins
Journal: Journal of Clinical Oncology (2023)

Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer.To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
An Update on Outcomes for COPD Pharmacological Trials: A COPD Investigators Report - Reassessment of the 2008 American Thoracic Society/European Respiratory Society Statement on Outcomes for COPD Pharmacological Trials
Authors: Mario Cazzola, Paola Rogliani, Peter J. Barnes, Francesco Blasi, Bartolome Celli, Nicola A. Hanania, Fernando J. Martinez, Bruce E. Miller, Marc Miravitlles, Clive P. Page, Ruth Tal-Singer, Maria Gabriella Matera
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Background: In 2008, a dedicated American Thoracic Society/European Respiratory Society task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in patients with chronic obstructive pulmonary disease. Since then, our scientific understanding of chronic obstructive pulmonary disease has increased considerably; there has been a progressive shift from a one-size-fits-all diagnostic and therapeutic approach to a personalized approach; and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. Objectives: The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report. Methods: The authors separately created search strategies for the literature, primarily based on their opinions and assessments supported by carefully chosen references. No centralized examination of the literature or uniform criteria for including or excluding evidence were used. Measurements and Main Results: Endpoints, outcomes, and biomarkers have been revisited. The limitations of some of those reported in the American Thoracic Society/European Respiratory Society task force document have been highlighted. In addition, new tools that may be useful, especially in evaluating personalized therapy, have been described. Conclusions: Because the "label-free" treatable traits approach is becoming an important step toward precision medicine, future clinical trials should focus on highly prevalent treatable traits, and this will influence the choice of outcomes and markers to be considered. The use of the new tools, particularly combination endpoints, could help better identify the right patients to be treated with the new drugs.
Biodegradable Piezoelectric Polymers: Recent Advancements in Materials and Applications
Authors: Mohsin Ali, Mohammad Javad Bathaei, Emin Istif, Seyed Nasir Hosseini Karimi, Levent Beker
Journal: Advanced Healthcare Materials (2023)

Recent materials, microfabrication, and biotechnology improvements have introduced numerous exciting bioelectronic devices based on piezoelectric materials. There is an intriguing evolution from conventional unrecyclable materials to biodegradable, green, and biocompatible functional materials. As a fundamental electromechanical coupling material in numerous applications, novel piezoelectric materials with a feature of degradability and desired electrical and mechanical properties are being developed for future wearable and implantable bioelectronics. These bioelectronics can be easily integrated with biological systems for applications, including sensing physiological signals, diagnosing medical problems, opening the blood-brain barrier, and stimulating healing or tissue growth. Therefore, the generation of piezoelectricity from natural and synthetic bioresorbable polymers has drawn great attention in the research field. Herein, the significant and recent advancements in biodegradable piezoelectric materials, including natural and synthetic polymers, their principles, advanced applications, and challenges for medical uses, are reviewed thoroughly. The degradation methods of these piezoelectric materials through in vitro and in vivo studies are also investigated. These improvements in biodegradable piezoelectric materials and microsystems could enable new applications in the biomedical field. In the end, potential research opportunities regarding the practical applications are pointed out that might be significant for new materials research.
Effectiveness of mRNA and inactivated COVID-19 vaccines: A test-negative study in an infection-naïve Hong Kong population
Authors: Rita W.Y. Ng, Ryan K.H. Sze, Ka Chun Chong, Shi Zhao, Lowell Ling, Grace Lui, Agnes S.Y. Leung, Apple C.M. Yeung, Wendy C.S. Ho, Martin C.S. Wong, Zigui Chen, Siaw S. Boon, David S.C. Hui, Paul K.S. Chan
Journal: Journal of Infection (2023)
Germline Exome Sequencing for Men with Testicular Germ Cell Tumor Reveals Coding Defects in Chromosomal Segregation and Protein-targeting Genes
Authors: Louise C. Pyle, Jung Kim, Jonathan Bradfield, Scott M. Damrauer, Kurt D'Andrea, Lawrence H. Einhorn, Rama Godse, Hakon Hakonarson, Peter A. Kanetsky, Rachel L. Kember, Linda A. Jacobs, Kara N. Maxwell, Daniel J. Rader, David J. Vaughn, Benita Weathers, Bradley Wubbenhorst, None Regeneron Genetics Center Research Team, None Cancer Genomics Research Laboratory, Mark H. Greene, Katherine L. Nathanson, Douglas R. Stewart
Journal: European Urology (2023)
Trends and perspectives for improving quality of chronic kidney disease care: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Authors: Kai-Uwe Eckardt, Cynthia Delgado, Hiddo J.L. Heerspink, Roberto Pecoits-Filho, Ana C. Ricardo, Bénédicte Stengel, Marcello Tonelli, Michael Cheung, Michel Jadoul, Wolfgang C. Winkelmayer, Holly Kramer, Ziyad Al-Aly, Gloria E. Ashuntantang, Peter Boor, Viviane Calice da Silva, Jill Coleman, Josef Coresh, Pierre Delanaye, Natalie Ebert, Philipp Enghard, Harold I. Feldman, Lori Fisher, Jennifer E. Flythe, Akira Fukui, Morgan E. Grams, Joseph H. Ix, Meg J. Jardine, Vivek Jha, Wenjun Ju, Robert Jurish, Robert Kalyesubula, Naoki Kashihara, Andrew S. Levey, Adeera Levin, Valerie Luyckx, Jolanta Małyszko, Jo-Anne Manski-Nankervis, Sankar D. Navaneethan, Greg Obrador, Alberto Ortiz, John Ortiz, Bento Fortunato Cardoso Dos Santos, Mark J. Sarnak, Elke Schaeffner, Nick M. Selby, David M. Simpson, Laura Solá, Wendy L. St. Peter, Paul E. Stevens, Navdeep Tangri, Elliot Koranteng Tannor, Irma Tchokhonelidze, Nicola Wilck, Michelle M.Y. Wong
Journal: Kidney International (2023)

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts of precision medicine for CKD identification and management continue to be developed, an ongoing discussion of the potential implications for care delivery is required. The 2022 KDIGO Controversies Conference on Improving CKD Quality of Care: Trends and Perspectives examined and discussed best practices for improving the precision of CKD diagnosis and prognosis, managing the complications of CKD, enhancing the safety of care, and maximizing patient quality of life. Existing tools and interventions currently available for the diagnosis and treatment of CKD were identified, with discussion of current barriers to their implementation and strategies for improving the quality of care delivered for CKD. Key knowledge gaps and areas for research were also identified.
Radionuclide‐Labeled Microspheres for Radio‐Immunotherapy of Hepatocellular Carcinoma
Authors: Sai Yang, Chongjing Mu, Teng Liu, Pei Pei, Wenhao Shen, Yanxiang Zhang, Guanglin Wang, Lei Chen, Kai Yang
Journal: Advanced Healthcare Materials (2023)

Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced hepatocellular carcinoma (HCC), but the inability of RSI and TARE to treat tumor metastasis and recurrence limits their benefits for patients in the clinic. Herein, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors-loaded alginate microspheres (IMs) are developed as radionuclide carriers with immunomodulatory functions to achieve effective radio-immunotherapy. The size and swelling properties of IMs can be facilely tailored by adjusting the calcium source during emulsification. Small/large IMs(SIMs/LIMs) are biocompatible and available for RSI and TARE, respectively, after 177 Lu labeling. Among them, 177 Lu-SIMs completely eliminated subcutaneous HCC in mice after intratumoral RSI. Moreover, in combination with anti-PD-L1, 177 Lu-SIMs not only eradicate primary tumors by RSI but also effectively inhibit the growth of distant tumors, wherein the potent abscopal effect can be ascribed to the immune stimulation of RSI and the modulation of the tumor immune microenvironment (TIME) by IDO1 inhibitors. In parallel, LIMs demonstrate excellent embolization efficiency, resulting in visible necrotic lesions in the central auricular artery of rabbits, which are promising for TARE in future studies. Collectively, a versatile therapeutic agent is provided to synchronously modulate the TIME during brachytherapy for efficient radio-immunotherapy of advanced HCC.
“We reduced sexual safety incidents with better reporting systems and talking to patients about sex”
Authors: Adele Waters, Ingrid Torjesen
Journal: BMJ (2023)

We reduced sexual safety incidents with better reporting systems and talking to patients about sex" Sexual safety leads Sally Ashton and Emma Furlong share their story as part of The BMJ and Guardian's investigation into sexual assault in the NHS Adele Waters, Ingrid Torjesen "When you make reporting clearer, you get an increase in reported incidents because people understand what they are reporting," says Sally Ashton, a nurse who leads on sexual safety at Gloucestershire Health and Care NHS Foundation Trust, a mental health and physical care provider.The trust introduced a sexual safety policy in January 2022 and changed the way that sexual safety incidents were reported so that staff understood what to report and what incidents were happening on wards.
IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation
Authors: Peyton E. Conrey, Lidiya Denu, Kaitlin C. O’Boyle, Isaiah Rozich, Jamal Green, Jeffrey Maslanka, Jean-Bernard Lubin, Tereza Duranova, Brittany L. Haltzman, Lauren Gianchetti, Derek A. Oldridge, Nina De Luna, Laura A. Vella, David Allman, Jonathan M. Spergel, Ceylan Tanes, Kyle Bittinger, Sarah E. Henrickson, Michael A. Silverman
Journal: Science Immunology (2023)

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have been proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on a larger scale, whether the systemic and mucosal anti-commensal responses are redundant or have unique features. To address this gap in knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry and metagenomic sequencing (mFLOW-Seq) to comprehensively define which microbes induce mucosal and systemic antibodies. We coupled this approach with high-dimensional immune profiling to study a cohort of pediatric patients with SIgAD and household control siblings. We found that mucosal and systemic antibody networks cooperate to maintain homeostasis by targeting a common subset of commensal microbes. In IgA-deficiency, we find increased translocation of specific bacterial taxa associated with elevated levels of systemic IgG targeting fecal microbiota. Associated features of immune system dysregulation in IgA-deficient mice and humans included elevated levels of inflammatory cytokines, enhanced follicular CD4 T helper cell frequency and activation, and an altered CD8 T cell activation state. Although SIgAD is clinically defined by the absence of serum IgA, the symptomatology and immune dysregulation were concentrated in the SIgAD participants who were also fecal IgA deficient. These findings reveal that mucosal IgA deficiency leads to aberrant systemic exposures and immune responses to commensal microbes, which increase the likelihood of humoral and cellular immune dysregulation and symptomatic disease in patients with IgA deficiency.
Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection
Authors: Matthieu Rousseau, Livia Lacerda Mariano, Tracy Canton, Molly A. Ingersoll
Journal: Science Immunology (2023)

Urinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early in infection, by reducing the inoculum or with antibiotics after infection, completely abrogated the protective memory response. We observed a mixed T helper (T H ) cell polarization, composed of T H 1, T H 2, and T H 17 T cells, among T cells infiltrating the bladder during primary infection. Thus, we hypothesized that reducing antigen load altered T H cell polarization, leading to poor memory. Unexpectedly, however, T H cell polarization was unchanged in these scenarios. Instead, we uncovered a population of tissue-resident memory (T RM ) T cells that was significantly reduced in the absence of sufficient antigen. Demonstrating that T RM cells are necessary for immune memory, transfer of lymph node– or spleen-derived infection-experienced T cells to naïve animals did not confer protection against infection. Supporting that T RM cells are sufficient to protect against recurrent UTI, animals depleted of systemic T cells, or treated with FTY720 to block memory lymphocyte migration from lymph nodes to infected tissue, were equally protected compared with unmanipulated mice against a second UTI. Thus, we uncovered an unappreciated key role for T RM cells in the memory response to bacterial infection in the bladder mucosa, providing a target for non–antibiotic-based immunotherapy and/or new vaccine strategies to prevent recurrent UTI.
Premenarchal lichen sclerosus: a multicentre examination of the novel diagnostic tool, the SWIFT model
Authors: Ashli Lawson, Michael Wininger, Melinda Wang, Makenna Steger, Kalie Peccerillo, Alla Vash-Margita
Journal: British Journal of Dermatology (2023)

This is a validating study of a novel diagnostic tool, SWIFT, for rapid and accurate diagnosis of prepubertal lichen sclerosus.
Labour’s promises on health are setting the party up to fail
Authors: Richard Vize
Journal: BMJ (2023)

Starmer is making big, conflicting, and unrealistic promises on health, without a clear plan for delivering them, which is setting Labour up to fail.In a speech at a Braintree ambulance station on Monday 22 May 2023, Starmer, leader of the Labour party, committed a Labour government to meeting a raft of targets that haven't been hit for years, saying, "Ambulances-seven minutes for cardiac arrest.A&E-back to the four hour target.GPs-the highest satisfaction levels on record.Waiting lists-down.Planned treatment within 18 weeks.No backsliding, no excuses-we will meet these standards again."
Rapid and Facile Light‐Based Approach to Fabricate Protease‐Degradable Poly(ethylene glycol)−norbornene Microgels for Cell Encapsulation
Authors: Ana Mora‐Boza, Saron G. Ghebrezadik, Johannes E. Leisen, Andrés J. García
Journal: Advanced Healthcare Materials (2023)

Thiol-norbornene photoclickable poly (ethylene glycol) (PEG)-based (PEG-NB) hydrogels are attractive biomaterials for cell encapsulation, drug delivery, and regenerative medicine applications. Although many crosslinking strategies and chemistries have been developed for PEG-NB bulk hydrogels, fabrication approaches of PEG-NB microgels have not been extensively explored. Here, a fabrication strategy for 4-arm amide-linked PEG-NB (PEG-4aNB) microgels using flow-focusing microfluidics for human mesenchymal stem/stromal cell (hMSCs) encapsulation is presented. PEG-4aNB photochemistry allows high-throughput, ultrafast generation, and cost-effective synthesis of monodispersed microgels (diameter 340 ± 18, 380 ± 24, and 420 ± 15 µm, for 6, 8, and 10 wt% of PEG-4aNB, respectively) using an in situ crosslinking methodology in a microfluidic device. PEG-4aNB microgels show in vitro degradability due to the incorporation of a protease-degradable peptide during photocrosslinking and encapsulated cells show excellent viability and metabolic activity for at least 13 days of culture. Furthermore, the secretory profile (i.e., MMP-13, ICAM-1, PD-L1, CXCL9, CCL3/MIP-1, IL-6, IL-12, IL-17E, TNF-α, CCL2/MCP-1) of encapsulated hMSCs shows increased expression in response to IFN-γ stimulation. Collectively, this work shows a versatile and facile approach for the fabrication of protease-degradable PEG-4aNB microgels for cell encapsulation.
Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8
Authors: Wan Du, Volkan Ergin, Corena Loeb, Mingqian Huang, Stewart Silver, Ariel Miura Armstrong, Zaohua Huang, Channabasavaiah B. Gurumurthy, Hinrich Staecker, Xuezhong Liu, Zheng-Yi Chen
Journal: Molecular Therapy (2023)

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3A306T/A306T mice of an average age of 18.5 months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation. Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3A306T/A306T mice of an average age of 18.5 months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.